Using the zebrafish (danio rerio) embryo, this Phase I SBIR proposal aims to analyze the effects of ethanol on embryonic development and to identify biomarkers of Fetal Alcohol Syndrome (FAS). Using subtractive library technology, Phase I research will isolate genes involved in ethanol induced toxicity. Advantages of the zebrafish include transparency which facilitates visual analysis, rapid embryogenesis, a morphological and molecular basis of tissue and organ development that are either identical or similar to other vertebrates including man, and the low cost of maintaining and breeding large numbers of zebrafish. Embryo drug exposure and RNA isolation for gene expression testing are also simple procedures. In addition, high throughput, automated drug screening is possible C using the zebrafish. An eventual application of our model is to develop an assay to identify potential pharmacological interventions for fetuses at risk for FAS. The zebrafish could be used to screen therapeutic compounds that either protect fetal tissue from alcohol-related damage or aid in the restoration of damaged tissue. I PROPOSED COMMERCIAL APPLICATIONS: By providing a rapid method for identifying potential pharmacological interventions for fetuses at risk for FAS, the zebrafish assay will help to streamline the development of drugs and treatment protocols for FAS.